That is not exactly what Patterson said even thoug
Post# of 155128
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Posted On: 09/07/2021 1:41:51 PM
Re: the lawman #102712
That is not exactly what Patterson said even though he did try to mislead. I will lay it out and more in his own words with commentary from me.
Patterson says he doesn't know because the RTF was never released but claims there was an issue with tropism. How does he know he didn't do the tropism testing. Testing was done since the beginning of both trials using the leading tropism assay out there.
It's possible that leronlimab may be somewhat directly antiviral through
the disruption of the PI3K/AKT/mTOR/4E-BP1 pathway. With the caspase being unable to cleave there will be no replication. Indirectly anti-viral by strengthening the immune system including increases in natural killer T-cells.
Patterson says leronlimab has no activity against viral replication. Since invasion of cells is necessary for HIV replication blocking that invasion is of course activity against HIV replication.
Except the FDA considers drop in viral load to be the key indicator for effectiveness and -
Something I can actually agree with. It is more than adequate when compared to maraviroc, 81% vs. 43%. What he doesn't seem to know is that the FDA insisted on 700mg for the BLA in February 2019. What would he have done file the BLA at 350mg and have the FDA refuse it?
He seems to be a bit confused about this. Latent cells are a fairly small amount of cells. You could see a very small spike in virus replication from latent cells but with 100% receptor occupancy there's no way for those recently replicated viruses to continue replication so the spike would be limited. Once again he argues there's nothing to decrease the viral load. Leronlimab's CCR5 blockade stops replication by denying the virus a place to replicate.
Nader confused tropism with receptor occupancy. Where did he get that they wanted to replace tropism with receptor occupancy? He seems to have made that up out of whole cloth. Neither the CMO of Cytodyn or the CRO would have confused the two.
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Number 1 there was an issue with tropism. Tropism was actually required in the BLA study if you look at the submission to the FDA. Tropism is on the viral side before you're enrolled in this trial you must have a viral isolate that uses CCR5 or why else use leronlimab. You have an X4 isolate like drug addicts have or latent disease you don't qualify because the drug will have no activity.
Patterson says he doesn't know because the RTF was never released but claims there was an issue with tropism. How does he know he didn't do the tropism testing. Testing was done since the beginning of both trials using the leading tropism assay out there.
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I think there's also a misnomer that leronlimab is actually anti-viral, it's not, it has no activity against HIV replication and all it does is it blocks news cells from being infected and that's extremely important.
It's possible that leronlimab may be somewhat directly antiviral through
the disruption of the PI3K/AKT/mTOR/4E-BP1 pathway. With the caspase being unable to cleave there will be no replication. Indirectly anti-viral by strengthening the immune system including increases in natural killer T-cells.
Patterson says leronlimab has no activity against viral replication. Since invasion of cells is necessary for HIV replication blocking that invasion is of course activity against HIV replication.
Quote:
But the proper metric for that would have been to look at the change in CD4 count over time. The drug failed the CD4 count would go down the drug was successful the CD4 count would be maintained. By using viral load in this trial it's analogous to using glucose for a cholesterol drug. This needed to be discussed with the FDA.
Except the FDA considers drop in viral load to be the key indicator for effectiveness and -
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CD4 cell count is a weak surrogate endpoint
CD4 as endpoint
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The other thing that needed to be discussed with the FDA is that the 350mg dose may be perfectly adequate. Because we published a paper in 1990 that showed that the amount of CCR5 on T-cells goes down with antiretroviral therapy. Therefore the requirement for drug would be far less in those on combination therapy which is the BLA. Monotherapy is a different story. That's why using monotherapy for dose justification makes no sense. They're not on anti-retroviral therapy they're really, really high levels of CCR5 on their cells. Thus requiring more drug. As you can see from some of the monotherapy data that's been released.
Something I can actually agree with. It is more than adequate when compared to maraviroc, 81% vs. 43%. What he doesn't seem to know is that the FDA insisted on 700mg for the BLA in February 2019. What would he have done file the BLA at 350mg and have the FDA refuse it?
Quote:
The problem is in monotherapy there's nothing keeping latently infected cells from making a virus and causing a spike in viral load just on leronlimab. And that can occur during infection, inflammation, many factors can go into play to increase the replication of latently infected cells in HIV. Yet there's nothing to decrease the viral load. Because leronlimab doesn't decrease the viral load it protects uninfected cells. So the design of all of this has been confounding.
He seems to be a bit confused about this. Latent cells are a fairly small amount of cells. You could see a very small spike in virus replication from latent cells but with 100% receptor occupancy there's no way for those recently replicated viruses to continue replication so the spike would be limited. Once again he argues there's nothing to decrease the viral load. Leronlimab's CCR5 blockade stops replication by denying the virus a place to replicate.
Quote:
The other confounding factor is there was a conference call in November of 2020 where it is very clear that Cytodyn confused tropism with receptor occupancy. Tropism is all about the virus, receptor occupancy is all about the cell. The thought that receptor occupancy could replace tropism which is what they wanted to do because tropism was $3,000 an assay is complete confusion.
Nader confused tropism with receptor occupancy. Where did he get that they wanted to replace tropism with receptor occupancy? He seems to have made that up out of whole cloth. Neither the CMO of Cytodyn or the CRO would have confused the two.
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